Nasal devices

ABSTRACT

A nasal delivery device for and method of delivering substance to a nasal airway of a subject, the delivery device comprising: a nosepiece for fitting to a nostril of a subject; a delivery unit comprising a substance supply unit and a nozzle unit including at least one nozzle fluidly connected to the substance supply unit for generating an aerosol spray for delivery to a nasal airway of the subject; and an aerosol interactor operable to interact with an aerosol spray as generated by the at least one nozzle.

The present invention relates to a nasal delivery device for and amethod of delivering substance, in particular one of a liquid, as asuspension or solution, or a powder containing a medicament, especiallysystemic or topical pharmaceuticals, or a vaccine to the nasal airway ofa subject.

Referring to FIG. 1, the nasal airway 1 comprises the two nasal cavities2, 3 separated by the nasal septum 4, which airway 1 includes numerousostia, such as the paranasal sinus ostia 5 connected to the paranasalsinuses 6 and the tubal ostia 7 connected to the tuba auditiva 8 and themiddle ears 9, and olfactory cells, and is lined by the nasal mucosa.The nasal airway 1 can communicate with the nasopharynx, the oral cavityand the lower airway, with the nasal airway 1 being in selectivecommunication with the anterior region of the nasopharynx and the oralcavity by opening and closing of the oropharyngeal velum.

There are many nasal conditions which require treatment. One suchcondition is nasal inflammation, specifically rhinitis, which can beallergic or non-allergic and is often associated with infection andprevents normal nasal function. By way of example, allergic andnon-allergic inflammation of the nasal airway can typically effectbetween 10 and 20% of the population, with nasal congestion of theerectile tissues of the nasal concha, lacrimation, secretion of waterymucus, sneezing and itching being the most common symptoms. As will beunderstood, nasal congestion impedes nasal breathing and promotes oralbreathing, leading to snoring and sleep disturbance. Other nasalconditions include nasal polyps which arise from the paranasal sinuses,hypertrophic adenoids, secretory otitis media, sinus disease and reducedolfaction.

In the treatment of certain nasal conditions, the topical administrationof medicaments is preferable, particularly where the nasal mucosa is theprime pathological pathway, such as in treating or relieving nasalcongestion. Medicaments that are commonly topically delivered includedecongestants, anti-histamines, cromoglycates, steroids and antibiotics.At present, among the known anti-inflammatory pharmaceuticals, topicalsteroids have been shown to have an effect on nasal congestion. Topicaldecongestants have also been suggested for use in relieving nasalcongestion. The treatment of hypertrophic adenoids and chronic secretoryotitis media using topical decongestants, steroids and anti-microbialagents, although somewhat controversial, has also been proposed.Further, the topical administration of pharmaceuticals has been used totreat or at least relieve symptoms of inflammation in the anteriorregion of the nasopharynx, the paranasal sinuses and the auditory tubes.

Medicaments can also be systemically delivered through the nasalpathway, the nasal pathway offering a good administration route for thesystemic delivery of pharmaceuticals, such as hormones, for example,oxytocin and calcitionin, and analgetics, such as anti-migrainecompositions, as the high blood flow and large surface area of the nasalmucosa advantageously provides for rapid systemic uptake.

Nasal delivery is also expected to be advantageous for theadministration of medicaments requiring a rapid onset of action, forexample, analgetics, anti-emetics, insulin, anti-epileptics, sedativesand hypnotica, and also other pharmaceuticals, for example,cardio-vascular drugs. It is envisaged that nasal administration willprovide for a fast onset of action, at a rate similar to that ofinjection and at a rate much faster than that of oral administration.Indeed, for the treatment of many acute conditions, nasal administrationis advantageous over oral administration, since gastric stasis canfurther slow the onset of action following oral administration.

It is also expected that nasal delivery could provide an effectivedelivery route for the administration of proteins and peptides asproduced by modern biotechnological techniques. For such substances, themetabolism in the intestines and the first-pass-effect in the liverrepresent significant obstacles for reliable and cost-efficientdelivery.

Furthermore, it is expected that nasal delivery using the nasal deliverytechnique of the present invention will prove effective in the treatmentof many common neurological diseases, such as Alzheimer's, Parkinson's,psychiatric diseases and intracerebral infections, where not possibleusing existing techniques. The nasal delivery technique of the presentinvention allows for delivery to the olfactory region, which region islocated in the superior region of the nasal cavities and represents theonly region where it is possible to circumvent the blood-to-brainbarrier (BBB) and enable communication with the cerebrospinal fluid(CSF) and the brain.

Also, it is expected that the nasal delivery technique of the presentinvention will allow for the effective delivery of vaccines.

Aside from the delivery of medicaments and vaccines, the irrigation ofthe nasal mucosa with liquids, in particular saline solutions, iscommonly practised to remove particles and secretions, as well as toimprove the mucociliary activity of the nasal mucosa. These solutionscan be used in combination with active pharmaceuticals.

For any kind of drug delivery, accurate and reliable dosing isessential, but it is of particular importance in relation to theadministration of potent drugs which have a narrow therapeutic window,drugs with potentially serious adverse effects and drugs for thetreatment of serious and life-threatening conditions. For someconditions, it is essential to individualize the dosage to theparticular situation, for example, in the case of diabetes mellitus. Fordiabetes, and, indeed, for many other conditions, the dosage of thepharmaceutical is preferably based on actual real-time measurements.Currently, blood samples are most frequently used, but the analysis ofmolecules in the exhalation breath of subjects has been proposed as analternative to blood analysis for several conditions. Breath analysis iscurrently used for the diagnosis of conditions such as helicobacterpylori infections which cause gastric ulcers.

WO-A-00/51672 discloses a delivery device for delivering substance, inparticular a medicament, in a bi-directional flow through the nasalcavities, that is, an air flow which passes into one nostril, around theposterior margin of the nasal septum and in the opposite direction outof the other nostril. This bi-directional air flow advantageously actsto stimulate the sensory nerves in the nasal mucosa, therebyconditioning the subject for the delivery and providing a morecomfortable delivery situation.

There are many kinds of existing delivery units which are capable ofdelivering an aerosol spray of substance as required for nasal delivery.Such delivery units include aerosol canisters as used in pressurizedmetered dose inhalers (pMDIs) and mechanical delivery pumps, such asliquid spray pumps.

These delivery units are well-developed, but, for the purposes of nasaldelivery, suffer from the particular disadvantages of not providingaerosol sprays which have an optimized particle size distribution andthe particles of the aerosol sprays being projected from the deliverynozzle with a delivery force which is such as not to allow for theaerosol spray to be readily entrained in a gas flow. Indeed, thedelivery forces are such that the particles of the aerosol spray wouldimpact, and collect, on any proximate surfaces.

In the field of inhalation technology, spacers have been developed as ameans of overcoming the particular problem caused by the speed of theparticles of delivered aerosol sprays. Spacers are essentially chambersinto which an aerosol spray is delivered and from which a subjectinhales.

It is an aim of the present invention to provide an improved nasaldelivery device for and a method of delivering substance to the nasalairway of a subject.

In one aspect the present invention provides a nasal delivery device fordelivering substance to a nasal airway of a subject, comprising: anosepiece for fitting to a nostril of a subject; a delivery unitcomprising a substance supply unit and a nozzle unit including at leastone nozzle fluidly connected to the substance supply unit for generatingan aerosol spray for delivery to a nasal airway of the subject; and anaerosol interactor operable to interact with an aerosol spray asgenerated by the at least one nozzle.

Preferably, the aerosol interactor is configured such that operationthereof is actuated prior to actuation of the delivery unit.

Preferably, the at least one nozzle is configured such as to deliver theaerosol spray towards the nosepiece.

In one embodiment the aerosol interactor comprises a flow director fordirecting an interacting gas flow at the aerosol spray such as tointeract with the same.

Preferably, the flow director includes at least one flow-directingchannel downstream of the at least one nozzle for directing aninteracting gas flow and delivering at least one interacting gas streamto interact with the aerosol spray.

More preferably, the at least one flow-directing channel has an annularoutlet disposed about a delivery path of the aerosol spray.

In one embodiment the at least one flow-directing channel is configuredsuch as to direct the at least one interacting gas stream substantiallyorthogonally to the delivery path of the aerosol spray.

In another embodiment the at least one flow-directing channel isconfigured such as to direct the at least one interacting gas stream ina direction inclined to the delivery path of the aerosol spray and awayfrom the nosepiece.

Preferably, the at least one flow-directing channel is an annular,frusto-conical channel configured to deliver a conical, annularinteracting gas stream to the delivery path of the aerosol spray.

More preferably, the at least one flow-directing channel is configuredsuch that an apex of the conical, annular interacting gas streamdelivered thereby is co-incident with the delivery path of the aerosolspray.

In one embodiment the delivery device further comprises: a chamber influid communication with the nosepiece; and wherein the flow directorincludes an annular flow channel for providing an annular gas flow overan inner periphery of the chamber.

Preferably, the chamber includes a flow deflector disposed at the innerperiphery thereof and downstream of the at least one nozzle which issuch as to obstruct the annular gas flow generated at the innerperiphery of the chamber and cause the same to be deflected inwardly andgenerate a turbulent zone downstream of the at least one nozzle.

More preferably, the flow deflector comprises an annular member.

Preferably, the flow director includes a plurality of flow-directingchannels in spaced relation downstream of the at least one nozzle fordirecting an interacting gas flow and delivering a plurality ofinteracting gas streams to interact with the aerosol spray.

Preferably, the delivery device further comprises: a mouthpiece throughwhich the subject in use exhales.

In one embodiment the mouthpiece is fluidly connected to the flowdirector such that at least part of the exhaled air flow provides theinteracting gas flow.

In another embodiment the delivery device further comprises: a gassupply unit for delivering a gas flow, the gas supply unit being fluidlyconnected to the flow director such that at least part of the deliveredgas flow provides the interacting gas flow.

In another embodiment the aerosol interactor comprises a movable elementdisposed downstream of the at least one nozzle.

Preferably, the aerosol interactor is disposed in opposed relation tothe at least one nozzle.

More preferably, the aerosol interactor is configured such as to presenta continuous surface to the aerosol spray.

Preferably, the aerosol interactor is disposed relative to the at leastone nozzle such that the aerosol spray is reflected thereby.

In one embodiment the movable element comprises a rotatable element.

In another embodiment the movable element comprises first and secondrotatable elements coupled so as to rotate in unison, the firstrotatable element including vanes oriented in one sense such as to berotated in one sense by a gas flow thereover, and the second rotatableelement being disposed downstream of the at least one nozzle andincluding vanes oriented in the other, opposite sense to the vanes ofthe first rotatable element such as to generate an interacting gas flowin an upstream direction towards the at least one nozzle on beingrotated in the one sense by rotation of the first rotatable element.

Preferably, the first rotatable element is disposed upstream of the atleast one nozzle.

In a further embodiment the nozzle unit includes a tubular element whichextends downstream of the at least one nozzle and includes a pluralityof apertures for providing a plurality of flow paths therethrough, andthe aerosol interactor comprises a rotatable element disposed at adownstream end of the tubular element, the rotatable element includingfirst, outer vanes oriented in one sense and disposed radially beyondthe tubular element such that the rotatable element is rotated in onesense by a gas flow thereover, and second, inner vanes oriented in theother, opposite sense to the outer vanes such as to generate aninteracting gas flow in an upstream direction towards the at least onenozzle with rotation of the rotatable element, which interacting gasflow is such as to interact with the aerosol spray and pass through theapertures in the tubular element.

In one embodiment the substance supply unit comprises an aerosolcanister.

In another embodiment the substance supply unit comprises a deliverypump.

Preferably, the delivery pump comprises a liquid spray pump.

In another aspect the present invention provides a method of deliveringsubstance to a nasal airway of a subject, comprising the steps offitting a nosepiece to a nostril of a subject; actuating a delivery unitto generate an aerosol spray from at least one nozzle for delivery to anasal airway of the subject; and operating an aerosol interactor tointeract with an aerosol spray as generated by the at least one nozzle.

Preferably, operation of the aerosol interactor is actuated prior toactuation of the delivery unit.

Preferably, the aerosol spray is delivered towards the nosepiece.

In one embodiment the aerosol interactor comprises a flow director, andthe step of operating the aerosol interactor comprises the step ofdirecting an interacting gas flow at the aerosol spray such as tointeract with the same.

Preferably, the flow director includes at least one flow-directingchannel downstream of the at least one nozzle, and the step of operatingthe aerosol interactor comprises the step of directing an interactinggas flow to deliver at least one interacting gas stream to interact withthe aerosol spray.

More preferably, the at least one flow-directing channel has an annularoutlet disposed about a delivery path of the aerosol spray.

In one embodiment the at least one interacting gas stream is directedsubstantially orthogonally to the delivery path of the aerosol spray.

In another embodiment the at least one interacting gas stream isdirected in a direction inclined to the delivery path of the aerosolspray and away from the nosepiece.

Preferably, the at least one interacting gas stream is a conical,annular interacting gas stream.

More preferably, an apex of the conical, annular interacting gas streamis co-incident with the delivery path of the aerosol spray.

In one embodiment the aerosol spray is delivered into a chamber in fluidcommunication with the nosepiece; and further comprising the step ofproviding an annular gas flow over an inner periphery of the chamber.

Preferably, the chamber includes a flow deflector disposed at the innerperiphery thereof and downstream of the at least one nozzle; and furthercomprising the step of obstructing the annular gas flow generated at theinner periphery of the chamber such as to cause the same to be deflectedinwardly and generate a turbulent zone downstream of the at least onenozzle.

More preferably, the flow deflector comprises an annular member.

Preferably, the flow director includes a plurality of flow-directingchannels in spaced relation downstream of the at least one nozzle; andthe step of operating the aerosol interactor comprises the step of:directing an interacting gas flow to deliver a plurality of interactinggas streams to interact with the aerosol spray.

Preferably, the method further comprises the step of the subjectexhaling through a mouthpiece.

In one embodiment the mouthpiece is fluidly connected to the flowdirector such that at least part of the exhaled air flow provides theinteracting gas flow.

In another embodiment the method further comprises the step of:supplying a gas flow from a gas supply unit, at least part of thesupplied gas flow being delivered to the flow director as theinteracting gas flow.

In another embodiment the aerosol interactor comprises a movable elementdisposed downstream of the at least one nozzle; and the step ofoperating the aerosol interactor comprises the step of moving themovable element downstream of the at least one nozzle such as tointeract with the aerosol spray.

Preferably, the aerosol interactor is disposed in opposed relation tothe at least one nozzle.

More preferably, the aerosol interactor is configured such as to presenta continuous surface to the aerosol spray.

Preferably, the aerosol interactor is disposed relative to the at leastone nozzle such that the aerosol spray is reflected thereby.

In one embodiment the movable element comprises a rotatable element.

In another embodiment the movable element comprises first and secondrotatable elements coupled so as to rotate in unison, the firstrotatable element including vanes oriented in one sense such as to berotated in one sense by a gas flow thereover, and the second rotatableelement being disposed downstream of the at least one nozzle andincluding vanes oriented in the other, opposite sense to the vanes ofthe first rotatable element such as to generate an interacting gas flowin an upstream direction towards the at least one nozzle on beingrotated in the one sense by rotation of the first rotatable element; andfurther comprising the step of driving a gas flow over the firstrotatable element such as to cause rotation of the same and therebyrotate the second rotatable element such as to generate an interactinggas flow in an upstream direction towards the at least one nozzle.

Preferably, the first rotatable element is disposed upstream of the atleast one nozzle.

In a further embodiment the step of actuating the delivery unit togenerate an aerosol spray comprises the step of actuating the deliveryunit to generate an aerosol spray from at least one nozzle into atubular element which extends downstream of the at least one nozzle, thetubular element including a plurality of apertures for providing aplurality of flow paths therethrough; the step of operating the aerosolinteractor comprises the step of moving a rotatable element disposed ata downstream end of the tubular element, the rotatable element includingfirst, outer vanes oriented in one sense and disposed radially beyondthe tubular element such that the rotatable element is rotated in onesense by a gas flow thereover, and second, inner vanes oriented in theother, opposite sense to the outer vanes such as to generate aninteracting gas flow in an upstream direction towards the at least onenozzle with rotation of the rotatable element; and further comprisingthe step of: driving a gas flow over the outer vanes of the rotatableelement to cause rotation of the same and thereby cause the inner vanesof the rotatable element to generate an interacting gas flow in anupstream direction towards the at least one nozzle, which interactinggas flow is such as to interact with the aerosol spray and pass throughthe apertures in the tubular element.

In one embodiment the aerosol spray is from an aerosol canister.

In another embodiment the aerosol spray is from a delivery pump.

Preferably, the delivery pump comprises a liquid spray pump.

Preferred embodiments of the present invention will now be describedhereinbelow by way of example only with reference to the accompanyingdrawings, in which:

FIG. 1 schematically illustrates the nasal airway of a human subject;

FIG. 2( a) illustrates a nasal delivery device in accordance with afirst embodiment of the present invention;

FIG. 2( b) illustrates the nasal delivery device of FIG. 2( a) in theactuated configuration;

FIG. 3( a) illustrates a nasal delivery device in accordance with asecond embodiment of the present invention;

FIG. 3( b) illustrates the nasal delivery device of FIG. 3( a) in theactuated configuration;

FIG. 4( a) illustrates a nasal delivery device in accordance with athird embodiment of the present invention;

FIG. 4( b) illustrates the nasal delivery device of FIG. 4( a) in theactuated configuration;

FIG. 5( a) illustrates a nasal delivery device in accordance with afourth embodiment of the present invention;

FIG. 5( b) illustrates the nasal delivery device of FIG. 5( a) in theactuated configuration;

FIG. 6( a) illustrates a nasal delivery device in accordance with afifth embodiment of the present invention;

FIG. 6( b) illustrates the nasal delivery device of FIG. 6( a) in theactuated configuration;

FIG. 7( a) illustrates a nasal delivery device in accordance with asixth embodiment of the present invention;

FIG. 7( b) illustrates the nasal delivery device of FIG. 7( a) in theactuated configuration;

FIG. 8( a) illustrates a nasal delivery device in accordance with aseventh embodiment of the present invention;

FIG. 8( b) illustrates the nasal delivery device of FIG. 8( a) in theactuated configuration;

FIG. 9( a) illustrates a nasal delivery device in accordance with aneighth embodiment of the present invention;

FIG. 9( b) illustrates one end view of the rotatable element of thenasal delivery device of FIG. 9( a);

FIG. 9( c) illustrates the nasal delivery device of FIG. 9( a) in theactuated configuration;

FIG. 10( a) illustrates a nasal delivery device in accordance with aninth embodiment of the present invention;

FIG. 10( b) illustrates one end view of the rotatable element of thenasal delivery device of FIG. 10( a);

FIG. 10( c) illustrates the nasal delivery device of FIG. 10( a) in theactuated configuration;

FIG. 11( a) illustrates a nasal delivery device in accordance with atenth embodiment of the present invention;

FIG. 11( b) illustrates one end view of the first rotatable element ofthe rotatable unit of the nasal delivery device of FIG. 11( a);

FIG. 11( c) illustrates one end view of the second rotatable element ofthe rotatable unit of the nasal delivery device of FIG. 11( a);

FIG. 11( d) illustrates the nasal delivery device of FIG. 11( a) in theactuated configuration;

FIG. 12( a) illustrates a nasal delivery device in accordance with aneleventh embodiment of the present invention;

FIG. 12( b) illustrates one end view of the rotatable element of thenasal delivery device of FIG. 12( a); and

FIG. 12( c) illustrates the nasal delivery device of FIG. 12( a) in theactuated configuration.

FIGS. 2( a) and (b) illustrate a nasal delivery device in accordancewith a first embodiment of the present invention.

The delivery device comprises a chamber 63, in this embodiment asubstantially tubular member, into which an aerosol spray is delivered,a nosepiece 65 for fitting to a nostril of a subject which is in fluidcommunication with the chamber 63 and disposed to one, the downstream,end of the chamber 63, and a mouthpiece 67 through which the subjectexhales and which is in fluid communication with the chamber 63.

The delivery device further comprises a delivery unit 69, in thisembodiment a breath-actuated unit, for delivering an aerosol spray ofsubstance into the chamber 63. The delivery unit 69 comprises a nozzleunit 71 which includes a nozzle 73 for delivering an aerosol spray ofsubstance, and a substance supply unit 75 for delivering a metered doseof substance to the nozzle unit 71.

In this embodiment the nozzle 73 of the nozzle unit 71 is directedtowards the nosepiece 65 and is disposed so as to be co-axial therewith.

In this embodiment the substance supply unit 75 is an aerosol canisterfor delivering a metered volume of a propellant, preferably ahydrofluoroalkane (HFA) propellant or the like, containing substance,typically a medicament, either as a suspension or solution.

In an alternative embodiment the substance supply unit 75 could comprisea mechanical delivery pump, in particular a liquid delivery pump or apowder delivery pump, which delivers metered doses of substance onactuation thereof.

The delivery unit 69 is primeable, in this embodiment by loading abiasing element, and includes a release mechanism, which, whentriggered, releases the biasing element and actuates the substancesupply unit 75 to deliver a metered dose of substance.

The delivery device further comprises a flow director 77 which isconfigured to direct at least part of a delivered gas flow, in thisembodiment an exhaled air flow, through the chamber 63 such as tointeract with an aerosol spray as generated from the nozzle 73 of thenozzle unit 71 on actuation of the substance supply unit 75, whereby anaerosol spray, when delivered from the nozzle 73, is acted upon by thedirected air flow such as to optimize characteristics of the particlesthereof, and in particular modify the particle size distribution of theparticles of the aerosol spray and decelerate the particles of theaerosol spray, which particles, once so optimized, are then entrained bythe air flow through the chamber 63.

The flow director 77 comprises at least one baffle 79, in thisembodiment a plurality of baffles 79, which defines at least oneflow-directing channel 81 forwardly of the nozzle 73 of the nozzle unit71, in this embodiment a plurality of flow-directing channels 81 inspaced relation forwardly of the nozzle 73 of the nozzle unit 71, fordirecting part of the exhaled air flow as at least one interacting airstream, in this embodiment a plurality of interacting air streams, tointeract with an aerosol spray as generated from the nozzle 73 of thenozzle unit 71.

In this embodiment the at least one flow-directing channel 81 has anannular outlet and is configured such as to direct the at least oneinteracting air stream substantially orthogonally to the direction ofdelivery of the aerosol spray as generated from the nozzle 73 of thenozzle unit 71.

In this embodiment the at least one baffle 79 is configured such as todefine an annular flow channel 83 at the inner periphery of the chamber63, which annular channel 83 is such that the other part of the exhaledair flow provides an annular air flow over the inner periphery of thechamber 63.

With this configuration, each interacting air stream in effect providesan air zone, akin to an air wall, through which an aerosol spray asgenerated from the nozzle 73 of the nozzle unit 71 has to penetrate.

Operation of the delivery device will now be described hereinbelow.

Firstly, the nosepiece 65 is fitted to a nostril of a subject and themouthpiece 67 is gripped in the lips of the subject.

The subject then begins to exhale through the mouthpiece 67, whichexhalation acts to close the oropharyngeal velum of the subject anddeliver an air flow through the chamber 63 and the nasal airway 1 of thesubject, part of which air flow is directed through the at least oneflow-directing channel 81 and delivered as at least one interacting airstream radially to the delivery path of an aerosol spray as generatedfrom the nozzle 73 of the nozzle unit 71 and the other part of which airflow flows through the annular flow channel 83 and provides an annularair flow over the inner periphery of the chamber 63.

When a predetermined flow rate is achieved through the chamber 63, thesubstance supply unit 75 is actuated to deliver a metered dose ofsubstance through the nozzle 73 of the nozzle unit 71, which nozzle 73generates an aerosol spray in a direction towards the nosepiece 65. Theaerosol spray, when delivered from the nozzle 73, is acted upon by theat least one interacting air flow such as to optimize characteristics ofthe particles of the aerosol spray, which particles, as so optimized,are then entrained by the air flow through the chamber 63.

In this way, the particles of the generated aerosol spray as deliveredto the nasal airway 1 have optimized characteristics, and in particulara modified particle size distribution and a much reduced velocity.Optimizing the particle size distribution of the aerosol spray providesfor improved delivery to targeted sites in the nasal airway. Indecelerating the particles of the aerosol spray, deposition on unwantedsurfaces, which would result where the particles are delivered directlyfrom the nozzle 73 of the nozzle unit 71 without intervention, isavoided.

FIGS. 3( a) and (b) illustrate a nasal delivery device in accordancewith a second embodiment of the present invention.

The delivery device of this embodiment is very similar to the deliverydevice of the above-described first embodiment, and thus, in order toavoid unnecessary duplication of description, only the differences willbe described in detail, with like reference signs designating likeparts.

The delivery device of this embodiment differs from that of theabove-described first embodiment in that the flow director 77 ismodified to omit the annular flow channel 83, whereby the entire exhaledair flow is directed through the at least one flow-directing channel 81.

Operation of the delivery device is the same as for the above-describedfirst embodiment, with the entire exhaled air flow being delivered tothe chamber 63, and hence the nasal airway 1, in response to exhalationthrough the mouthpiece 67.

FIGS. 4( a) and (b) illustrate a nasal delivery device in accordancewith a third embodiment of the present invention.

The delivery device of this embodiment is very similar to the deliverydevice of the above-described first embodiment, and thus, in order toavoid unnecessary duplication of description, only the differences willbe described in detail, with like reference signs designating likeparts.

The delivery device of this embodiment differs from that of theabove-described first embodiment in further comprising an exhalationbreath actuatable gas supply unit 85 for delivering a gas flow to thechamber 63 in response to exhalation by a subject, and in that themouthpiece 67 is in fluid communication with the gas supply unit 85 andnot the chamber 63, whereby a gas flow is delivered to the chamber 63,and hence the nasal airway 1, in response to exhalation through themouthpiece 67.

Operation of the delivery device is the same as for the above-describedfirst embodiment, with a gas flow being delivered to the chamber 63, andhence the nasal airway 1, in response to exhalation through themouthpiece 67.

FIGS. 5( a) and (b) illustrate a nasal delivery device in accordancewith a fourth embodiment of the present invention.

The delivery device comprises a chamber 93, in this embodiment asubstantially tubular member, into which an aerosol spray is delivered,a nosepiece 95 for fitting to a nostril of a subject which is in fluidcommunication with the chamber 93 and disposed to one, the downstream,end of the chamber 93, and a mouthpiece 97 through which the subjectexhales and which is in fluid communication with the chamber 93.

The delivery device further comprises a delivery unit 99, in thisembodiment a breath-actuated unit, for delivering an aerosol spray ofsubstance into the chamber 93. The delivery unit 99 comprises a nozzleunit 101 which includes a nozzle 103 for delivering an aerosol spray ofsubstance, and a substance supply unit 105 for delivering a metered doseof substance to the nozzle unit 101.

In this embodiment the nozzle 103 of the nozzle unit 101 is directedtowards the nosepiece 95 and is disposed so as to be co-axial therewith.

In this embodiment the substance supply unit 105 is an aerosol canisterfor delivering a metered volume of a propellant, preferably ahydrofluoroallcane (HFA) propellant or the like, containing substance,typically a medicament, either as a suspension or solution.

In an alternative embodiment the substance supply unit 105 couldcomprise a mechanical delivery pump, in particular a liquid deliverypump or a powder delivery pump, which delivers metered doses ofsubstance on actuation thereof.

The delivery unit 99 is primeable, in this embodiment by loading abiasing element, and includes a release mechanism, which, whentriggered, releases the biasing element and actuates the substancesupply unit 105 to deliver a metered dose of substance.

The delivery device further comprises a flow director 107 which isconfigured to direct a delivered gas flow, in this embodiment an exhaledair flow, through the chamber 93 such as to interact with an aerosolspray as generated from the nozzle 103 of the nozzle unit 101 onactuation of the substance supply unit 105, whereby an aerosol spray,when delivered from the nozzle 103, is acted upon by the directed airflow such as to optimize characteristics of the particles thereof, andin particular modify the particle size distribution of the particles ofthe aerosol spray and decelerate the particles of the aerosol spray,which particles, once so optimized, are then entrained by the air flowthrough the chamber 93.

The flow director 107 comprises at least one baffle 109, in thisembodiment a plurality of baffles 109, which defines at least oneflow-directing channel 111 forwardly of the nozzle 103 of the nozzleunit 101, in this embodiment a single flow-directing channel 111, fordirecting at least part of the exhaled air flow as at least oneinteracting air stream, in this embodiment a single interacting airstream, to interact with an aerosol spray as generated from the nozzle103 of the nozzle unit 101.

In this embodiment the at least one flow-directing channel 111 has anannular outlet and is configured such as to direct the at least oneinteracting air stream in a direction inclined to the direction ofdelivery of an aerosol spray as generated from the nozzle 103 of thenozzle unit 101 and away from the nosepiece 95.

In this embodiment the at least one flow-directing channel 111 is anannular, frusto-conical channel, here of narrowing section towards theoutlet thereof, which delivers a conical, annular interacting air streamto the delivery path of an aerosol spray as generated from the nozzle103 of the nozzle unit 101. In this embodiment the apex of the conical,annular interacting air stream is co-incident with the delivery path ofan aerosol spray as generated from the nozzle 103 of the nozzle unit101.

With this configuration, the interacting air stream in effect providesan air zone, akin to an air wall, through which an aerosol spray asgenerated from the nozzle 103 of the nozzle unit 101 has to penetrate.

Operation of the delivery device will now be described hereinbelow.

Firstly, the nosepiece 95 is fitted to a nostril of a subject and themouthpiece 97 is gripped in the lips of the subject.

The subject then begins to exhale through the mouthpiece 97, whichexhalation acts to close the oropharyngeal velum of the subject anddeliver an air flow through the chamber 93 and the nasal airway 1 of thesubject, which air flow is directed through the at least oneflow-directing channel 111 and delivered as at least one conical,annular interacting air stream to the delivery path of an aerosol sprayas generated from the nozzle 103 of the nozzle unit 101.

When a predetermined flow rate is achieved through the chamber 93, thesubstance supply unit 105 is actuated to deliver a metered dose ofsubstance through the nozzle 103 of the nozzle unit 101, which nozzle103 generates an aerosol spray in a direction towards the nosepiece 95.The aerosol spray, when delivered from the nozzle 103, is acted upon bythe at least one interacting gas stream such as to optimizecharacteristics of the particles of the aerosol spray, which particles,as so optimized, are then entrained by the air flow through the chamber93.

In this way, the particles of the generated aerosol spray as deliveredto the nasal airway 1 have optimized characteristics, and in particulara modified particle size distribution and a much reduced velocity.Optimizing the particle size distribution of the aerosol spray providesfor improved delivery to targeted sites in the nasal airway. Indecelerating the particles of the aerosol spray, deposition on unwantedsurfaces, which would result where the particles are delivered directlyfrom the nozzle 103 of the nozzle unit 101 without intervention, isavoided.

FIGS. 6( a) and (b) illustrate a nasal delivery device in accordancewith a fifth embodiment of the present invention.

The delivery device comprises a chamber 93, in this embodiment asubstantially tubular member, into which an aerosol spray is delivered,a nosepiece 95 for fitting to a nostril of a subject which is in fluidcommunication with the chamber 93 and disposed to one, the downstream,end of the chamber 93, and a mouthpiece 97 through which the subjectexhales and which is in fluid communication with the chamber 93.

The delivery device further comprises a delivery unit 99, in thisembodiment a breath-actuated unit, for delivering an aerosol spray ofsubstance into the chamber 93. The delivery unit 99 comprises a nozzleunit 101 which includes a nozzle 103 for delivering an aerosol spray ofsubstance, and a substance supply unit 105 for delivering a metered doseof substance to the nozzle unit 101.

In this embodiment the nozzle 103 of the nozzle unit 101 is directedtowards the nosepiece 95 and disposed so as to be co-axial therewith.

In this embodiment the substance supply unit 105 is an aerosol canisterfor delivering a metered volume of a propellant, preferably ahydrofluoroalkane (HFA) propellant or the like, containing substance,typically a medicament, either as a suspension or solution. In analternative embodiment the substance supply unit 105 could comprise amechanical delivery pump, in particular a liquid delivery pump or apowder delivery pump, which delivers metered doses of substance onactuation thereof.

The delivery unit 99 is primeable, in this embodiment by loading abiasing element, and includes a release mechanism, which, whentriggered, releases the biasing element and actuates the substancesupply unit 105 to deliver a metered dose of substance.

The delivery device further comprises a flow director unit 106 fordirecting an interacting gas flow, separate to the exhalation breath ofa subject, into the chamber 93 such as to interact with an aerosol sprayas generated from the nozzle 103 of the nozzle unit 101 on actuation ofthe substance supply unit 105, whereby an aerosol spray, when deliveredfrom the nozzle 103, is acted upon by the directed gas flow such as tooptimize characteristics of the particles thereof, which particles, onceso optimized, are then entrained by a gas flow, in this embodiment theexhalation air flow, through the chamber 93.

The flow director unit 106 comprises a flow director 107 which isconfigured to direct an interacting gas flow to the delivery path of anaerosol spray as generated from the nozzle 103 of the nozzle unit 101 onactuation of the substance supply unit 105, and a gas supply unit 108which is actuatable to deliver a gas flow to the flow director 107.

In this embodiment the flow director 107 comprises a plurality ofbaffles 109 which define a plurality of flow-directing channels 111 inspaced relation forwardly of the nozzle 103 of the nozzle unit 101 fordirecting a plurality of interacting gas streams to the delivery path ofan aerosol spray as generated from the nozzle 103 of the nozzle unit 101on actuation of the substance supply unit 105.

In this embodiment the flow-directing channels 111 each have an annularoutlet and are configured such as to direct an interacting gas stream ina direction inclined to the direction of delivery of an aerosol spray asgenerated from the nozzle 103 of the nozzle unit 101 and away from thenosepiece 95.

In this embodiment the flow-directing channels 111 are annular,frusto-conical channels, each of narrowing section towards therespective outlets thereof, which deliver conical, annular interactinggas streams to the delivery path of an aerosol spray as generated fromthe nozzle 103 of the nozzle unit 101. In this embodiment the apexes ofthe conical, annular interacting gas streams are co-incident with thedelivery path of an aerosol spray as generated from the nozzle 103 ofthe nozzle unit 101.

With this configuration, the interacting gas streams each in effectprovide a gas zone, akin to a gas wall, through which an aerosol sprayas generated from the nozzle 103 of the nozzle unit 101 has topenetrate.

Operation of the delivery device will now be described hereinbelow.

Firstly, the nosepiece 95 is fitted to a nostril of a subject and themouthpiece 97 is gripped in the lips of the subject.

The subject then begins to exhale through the mouthpiece 97, whichexhalation acts to close the oropharyngeal velum of the subject anddeliver an air flow through the chamber 93 and the nasal airway 1 of thesubject, which air flow acts to actuate the gas supply unit 108 todeliver an interacting gas flow to the flow-directing channels 111,which interacting gas flow is directed through the flow-directingchannels 111 and delivered as conical, annular interacting gas streamsto the delivery path of an aerosol spray as generated from the nozzle103 of the nozzle unit 101.

When a predetermined flow rate is achieved through the chamber 93, thesubstance supply unit 105 is actuated to deliver a metered dose ofsubstance through the nozzle 103 of the nozzle unit 101, which nozzle103 generates an aerosol spray in a direction towards the nosepiece 95.The aerosol spray, when delivered from the nozzle 103, is acted upon bythe interacting gas streams in succession such as to optimizecharacteristics of particles of the aerosol spray, which particles, asso optimized, are then entrained by the air flow through the chamber 93.

In this way, the particles of the generated aerosol spray as deliveredto the nasal airway 1 have optimized characteristics, and in particulara modified particle size distribution and a much reduced velocity.Optimizing the particle size distribution of the aerosol spray providesfor improved delivery to targeted sites in the nasal airway. Indecelerating the particles of the aerosol spray, deposition on unwantedsurfaces, which would result where the particles are delivered directlyfrom the nozzle 103 of the nozzle unit 101 without intervention, isavoided.

FIGS. 7( a) and (b) illustrate a nasal delivery device in accordancewith a sixth embodiment of the present invention.

The delivery device comprises a chamber 133, in this embodiment asubstantially tubular member, into which an aerosol spray is delivered,a nosepiece 135 for fitting to a nostril of a subject which is in fluidcommunication with the chamber 133 and disposed to one, the downstream,end of the chamber 133, and a mouthpiece 137 through which the subjectexhales and which is in fluid communication with the chamber 133.

The delivery device further comprises a delivery unit 139, in thisembodiment a breath-actuated unit, for delivering an aerosol spray ofsubstance into the chamber 133. The delivery unit 139 comprises a nozzleunit 141 which includes a nozzle 143 for delivering an aerosol spray ofsubstance, and a substance supply unit 145 for delivering a metered doseof substance to the nozzle unit 141.

In this embodiment the nozzle 143 of the nozzle unit 141 is directedtowards the nosepiece 135 and disposed so as to be co-axial therewith.

In this embodiment the substance supply unit 145 is an aerosol canisterfor delivering a metered volume of a propellant, preferably ahydrofluoroalkane (HFA) propellant or the like, containing substance,typically a medicament, either as a suspension or solution.

In an alternative embodiment the substance supply unit 145 couldcomprise a mechanical to delivery pump, in particular a liquid deliverypump or a powder delivery pump, which delivers metered doses ofsubstance on actuation thereof.

The delivery unit 139 is primeable, in this embodiment by loading abiasing element, and includes a release mechanism, which, whentriggered, releases the biasing element and actuates the substancesupply unit 145 to deliver a metered dose of substance.

The delivery device further comprises a flow director 147 which isconfigured to direct part of a delivered gas flow, in this embodiment anexhaled air flow, through the chamber 133 such as to interact with anaerosol spray as generated from the nozzle 143 of the nozzle unit 141 onactuation of the substance supply unit 145, whereby an aerosol spray,when delivered from the nozzle 143, is acted upon by the directed airflow such as to optimize characteristics of the particles thereof, andin particular modify the particle size distribution of the aerosol sprayand decelerate the particles of the aerosol spray, which particles, onceso optimized, are then entrained by the air flow through the chamber133.

The flow director 147 includes at least one flow-directing channel 151,in this embodiment a single flow-directing channel 151, for directingpart of the delivered air flow to interact with an aerosol spray asgenerated from the nozzle 143 of the nozzle unit 141. In an alternativeembodiment the flow director 147 could include a plurality offlow-directing channels 151.

In this embodiment the at least one flow-directing channel 151 has anannular outlet and is configured such as to direct the at least oneinteracting air stream in a direction inclined to the direction ofdelivery of an aerosol spray as generated from the nozzle 143 of thenozzle unit 141 and away from the nosepiece 135.

In this embodiment the at least one flow-directing channel 151 is anannular, frusto-conical channel, here of narrowing section towards theoutlet thereof, which delivers a conical, annular interacting air streamto the delivery path of an aerosol spray as generated from the nozzle143 of the nozzle unit 141. In this embodiment the apex of the conical,annular interacting air stream is co-incident with the delivery path ofan aerosol spray as generated from the nozzle 143 of the nozzle unit141.

With this configuration, the interacting air stream in effect providesan air zone, akin to an air wall, through which an aerosol spray asgenerated from the nozzle 143 of the nozzle unit 141 has to penetrate.

In this embodiment the nozzle 143 of the nozzle unit 141 is shieldedsuch that the interacting air flow is provided entirely by the at leastone interacting air stream which is delivered through the at least oneflow-directing channel 151.

In this embodiment the flow director 147 further includes an annularflow channel 153 at the inner periphery of the chamber 133, whichannular channel 153 is such that the other part of the delivered airflow provides an annular air flow over the inner periphery of thechamber 133.

In this embodiment the chamber 133 includes a flow deflector 155, herean annular member, disposed about the inner periphery thereof downstreamof the nozzle 143 of the nozzle unit 141, which flow deflector 155 islocated such as to obstruct the annular air flow generated at the innerperiphery of the chamber 133 and cause the annular air flow to bedeflected inwardly and generate a turbulent zone ahead of the nozzle 143which further interacts with the aerosol spray as generated.

Operation of the delivery device will now be described hereinbelow.

Firstly, the nosepiece 135 is fitted to a nostril of a subject and themouthpiece 137 is gripped in the lips of the subject.

The subject then begins to exhale through the mouthpiece 137, whichexhalation acts to close the oropharyngeal velum of the subject anddeliver an air flow through the chamber 133 and the nasal airway 1 ofthe subject, part of which air flow is directed through the at least oneflow-directing channel 151 and delivered as at least one interacting airstream to the delivery path of an aerosol spray as generated from thenozzle 143 of the nozzle unit 141, in this embodiment towards the rootof the aerosol spray, and the other part of which air flow flows throughthe annular flow channel 153 and provides an annular air flow over theinner periphery of the chamber 133.

When a predetermined flow rate is achieved through the chamber 133, thesubstance supply unit 145 is actuated to deliver a metered dose ofsubstance through the nozzle 143 of the nozzle unit 141, which nozzle143 generates an aerosol spray in a direction towards the nosepiece 135.The aerosol spray, when delivered from the nozzle 143, is acted upon bythe at least one interacting air stream such as to optimizecharacteristics of the particles of the aerosol spray, which particles,as so optimized, are then entrained by the air flow through the chamber133.

In this way, the particles of the generated aerosol spray as deliveredto the nasal airway 1 have optimized characteristics, and in particulara modified particle size distribution and a much reduced velocity.Optimizing the particle size distribution of the aerosol spray providesfor improved delivery to targeted sites in the nasal airway. Indecelerating the particles of the aerosol spray, deposition on unwantedsurfaces, which would result where the particles are delivered directlyfrom the nozzle 143 of the nozzle unit 141 without intervention, isavoided.

FIGS. 8( a) and (b) illustrate a nasal delivery device in accordancewith a seventh embodiment of the present invention.

The delivery device comprises a chamber 163, in this embodiment asubstantially tubular member, into which an aerosol spray is delivered,a nosepiece 165 for fitting to a nostril of a subject which is in fluidcommunication with the chamber 163 and disposed to one, the downstream,end of the chamber 163, and a mouthpiece unit 166. In this embodimentthe delivery device is configured such as to provide no fluidcommunication path between the mouthpiece unit 166 and the chamber 163.

The mouthpiece unit 166 includes a mouthpiece 167 which is gripped bythe lips of the subject, and an exhalation breath sensor 168 which isfluidly connected to the mouthpiece 167, in this embodiment fordetecting the flow rate of the oral exhalation breath through themouthpiece unit 166. In an alternative embodiment the exhalation breathsensor 168 can be configured to detect a pressure developed in themouthpiece unit 166. In another alternative embodiment the exhalationbreath sensor 168 can be configured to detect both the flow rate of theoral exhalation breath and the pressure developed in the mouthpiece unit166.

The delivery device further comprises a delivery unit 169 for deliveringan aerosol spray of substance into the chamber 163. The delivery unit169 comprises a nozzle unit 171 which includes a nozzle 173 fordelivering an aerosol spray of substance, and a substance supply unit175 for delivering a metered dose of substance to the nozzle unit 171.

In this embodiment the nozzle 173 of the nozzle unit 171 is directedtowards the nosepiece 165 and disposed so as to be co-axial therewith.

In this embodiment the substance supply unit 175 is an aerosol canisterfor delivering a metered volume of a propellant, preferably ahydrofluoroalkane (HFA) propellant or the like, containing substance,typically a medicament, either as a suspension or solution.

In an alternative embodiment the substance supply unit 175 couldcomprise a mechanical delivery pump, in particular a liquid deliverypump or a powder delivery pump, which delivers metered doses ofsubstance on actuation thereof.

The delivery unit 169 is primeable, in this embodiment by loading abiasing element, and includes a release mechanism, which, whentriggered, releases the biasing element and actuates the substancesupply unit 175 to deliver a metered dose of substance.

The delivery device further comprises a gas supply unit 176 which isactuatable to deliver a gas flow to the chamber 163, as will bedescribed in more detail hereinbelow.

The delivery device further comprises a flow director 177 which isfluidly connected to the gas supply unit 176 for directing aninteracting gas flow, separate to the exhalation breath of a subject,into the chamber 163 such as to interact with an aerosol spray asgenerated from the nozzle 173 of the nozzle unit 171 on actuation of thesubstance supply unit 175, whereby an aerosol spray, when delivered fromthe nozzle 173, is acted upon by the interacting gas flow such as tooptimize characteristics of the particles thereof, and in particularmodify the particle size distribution of the particles of the aerosolspray and decelerate the particles of the aerosol spray, whichparticles, once so optimized, are then entrained through the chamber163.

In this embodiment the flow director 177 includes a plurality offlow-directing channels 181 in spaced relation forwardly of the nozzle173 of the nozzle unit 171 for directing the delivered gas flow as aplurality of interacting gas streams to the delivery path of an aerosolspray as generated from the nozzle 173 of the nozzle unit 171 onactuation of the substance supply unit 175.

In this embodiment the flow-directing channels 181 each have an annularoutlet and are configured such as to direct an interacting gas stream ina direction inclined to the direction of delivery of an aerosol spray asgenerated from the nozzle 173 of the nozzle unit 171 and away from thenosepiece 165.

In this embodiment the flow-directing channels 181 are annular,frusto-conical channels, each of narrowing section towards therespective outlets thereof, which deliver conical, annular interactinggas streams to the delivery path of an aerosol spray as generated fromthe nozzle 173 of the nozzle unit 171. In this embodiment the apexes ofthe conical, annular interacting gas streams are co-incident with thedelivery path of an aerosol spray as generated from the nozzle 173 ofthe nozzle unit 171.

With this configuration, the interacting gas streams each in effectprovide a gas zone, akin to a gas wall, through which an aerosol sprayas generated from the nozzle 173 of the nozzle unit 171 has topenetrate.

Operation of the delivery device will now be described hereinbelow.

Firstly, the nosepiece 165 is fitted to a nostril of a subject and themouthpiece 167 is gripped in the lips of the subject.

The subject then begins to exhale through the mouthpiece 167 of themouthpiece unit 166, which exhalation acts to close the oropharyngealvelum of the subject.

On generation of one or both of a predetermined pressure and flow ratethrough the mouthpiece unit 166, as detected by the exhalation breathsensor 168, the gas supply unit 176 is actuated to deliver a gas flowthrough the chamber 163 and the nasal airway 1 of the subject, which gasflow is directed through the flow-directing channels 181 and deliveredas conical, annular interacting gas streams to the delivery path of anaerosol spray as generated from the nozzle 173 of the nozzle unit 171.

In this embodiment, when a predetermined flow rate is achieved throughthe chamber 163, and hence the nasal airway 1, the substance supply unit175 is actuated to deliver a metered dose of substance through thenozzle 173 of the nozzle unit 171, which nozzle 173 generates an aerosolspray in a direction towards the nosepiece 165. The aerosol spray, whendelivered from the nozzle 173, is acted upon by the interacting gasstreams such as to optimize characteristics of the particles of theaerosol spray, which particles, as so optimized, are then entrained bythe gas flow through the chamber 163.

In alternative embodiments the substance supply unit 175 can beconfigured such as to be actuated in response to the generation of apredetermined pressure or both a predetermined pressure and flow rate inthe chamber 163.

In this way, the particles of the generated aerosol spray as deliveredto the nasal airway 1 have optimized characteristics, and in particulara modified particle size distribution and a much reduced velocity.Optimizing the particle size distribution of the aerosol spray providesfor improved delivery to targeted sites in the nasal airway. Indecelerating the particles of the aerosol spray, deposition on unwantedsurfaces, which would result where the particles are delivered directlyfrom the nozzle 173 of the nozzle unit 171 without intervention, isavoided.

FIGS. 9( a) to (c) illustrate a nasal delivery device in accordance withan eighth embodiment of the present invention.

The delivery device comprises a chamber 193, in this embodiment asubstantially tubular member, into which an aerosol spray is delivered,a nosepiece 195 for fitting to a nostril of a subject which is in fluidcommunication with the chamber 193 and disposed to one, the downstream,end of the chamber 193, and a mouthpiece 197 through which the subjectexhales and which is in fluid communication with the chamber 193.

The delivery device further comprises a delivery unit 199, in thisembodiment a breath-actuated unit, for delivering an aerosol spray ofsubstance into the chamber 193. The delivery unit 199 comprises a nozzleunit 201 which includes a nozzle 203 for delivering an aerosol spray ofsubstance, and a substance supply unit 205 for delivering a metered doseof substance to the nozzle unit 201.

In this embodiment the nozzle 203 of the nozzle unit 201 is directedtowards the nosepiece 195 and is disposed so as to be co-axialtherewith.

In this embodiment the substance supply unit 205 is an aerosol canisterfor delivering a metered volume of a propellant, preferably ahydrofluoroalkane (HFA) propellant or the like, containing substance,typically a medicament, either as a suspension or solution.

In an alternative embodiment the substance supply unit 205 couldcomprise a mechanical delivery pump, in particular a liquid deliverypump or a powder delivery pump, which delivers metered doses ofsubstance on actuation thereof.

The delivery unit 199 is primeable, in this embodiment by loading abiasing element, and includes a release mechanism, which, whentriggered, releases the biasing element and actuates the substancesupply unit 205 to deliver a metered dose of substance.

The delivery device further comprises a moving element 207 which isdisposed to downstream of and opposes the nozzle 203 of the nozzle unit201 such as to interact with an aerosol spray as generated from thenozzle 203, whereby an aerosol spray, when delivered from the nozzle203, is acted upon by the moving element 207, in this embodiment atleast in part by reflection from the surface of the moving element 207,such as to optimize characteristics of the aerosol spray, and inparticular modify the particle size distribution of the particles of theaerosol spray and decelerate particles of the aerosol spray, whichparticles, once so optimized, are then entrained by the air flow throughthe chamber 193.

In this embodiment the moving element 207 comprises a rotatable elementwhich is mounted about a central pivot 211 and includes a plurality ofinclined vanes 213 such as to be rotated by the action of a deliveredgas flow, in this embodiment an exhaled air flow, over the vanes 213. Inthis embodiment the vanes 213 of the moving element 207 are configuredsuch as to present a continuous surface to an aerosol spray as generatedfrom the nozzle 203 of the nozzle unit 201, and thereby no direct pathto the nosepiece 195.

Operation of the delivery device will now be described hereinbelow.

Firstly, the nosepiece 195 is fitted to a nostril of a subject and themouthpiece 197 is gripped in the lips of the subject.

The subject then begins to exhale through the mouthpiece 197, whichexhalation acts to close the oropharyngeal velum of the subject anddeliver an air flow through the chamber 193 and the nasal airway 1 ofthe subject, which air flow acts to rotate the movable element 207.

When a predetermined flow rate is achieved through the chamber 193, thesubstance supply unit 205 is actuated to deliver a metered dose ofsubstance through the nozzle 203 of the nozzle unit 201, which nozzle203 generates an aerosol spray in a direction towards the nosepiece 195.The aerosol spray, when delivered from the nozzle 195, is acted upon bythe movable element 207 such as to optimize characteristics of theparticles of the aerosol spray, which particles, as so optimized, arethen entrained by the air flow through the chamber 193.

In this way, the particles of the generated aerosol spray as deliveredto the nasal airway 1 have optimized characteristics, and in particularan optimized particle size distribution and a much reduced velocity.Optimizing the particle size distribution of the aerosol spray providesfor improved delivery to targeted sites in the nasal airway. Indecelerating the particles of the aerosol spray, deposition on unwantedsurfaces, which would result where the particles are delivered directlyfrom the nozzle 203 of the nozzle unit 201 without intervention, isavoided.

FIGS. 10( a) to (c) illustrate a nasal delivery device in accordancewith a ninth embodiment of the present invention.

The delivery device of this embodiment is very similar to the deliverydevice of the above-described eighth embodiment, and thus, in order toavoid unnecessary duplication of description, only the differences willbe described in detail, with like reference signs designating likeparts.

The delivery device of this embodiment differs from that of theabove-described eighth embodiment in further comprising an exhalationbreath actuatable gas delivery unit 214 for delivering a gas flow to thechamber 193 in response to exhalation by a subject, and in that themouthpiece 197 is in fluid communication with the gas delivery unit 214and not the chamber 193, whereby a gas flow is delivered to the chamber193, and hence the nasal airway 1, in response to exhalation through themouthpiece 197.

Operation of the delivery device is the same as for the above-describedeighth embodiment, with a gas flow being delivered to the chamber 193,and hence the nasal airway 1, in response to exhalation through themouthpiece 197.

FIGS. 11( a) to (d) illustrate a nasal delivery device in accordancewith a tenth embodiment of the present invention.

The delivery device comprises a chamber 223, in this embodiment asubstantially tubular member, into which an aerosol spray is delivered,a nosepiece 225 for fitting to a nostril of a subject which is in fluidcommunication with the chamber 223 and disposed to one, the downstream,end of the chamber 223, and a mouthpiece 227 through which the subjectexhales and which is in fluid communication with the chamber 223.

The delivery device further comprises a delivery unit 229, in thisembodiment a breath-actuated unit, for delivering an aerosol spray ofsubstance into the chamber 223. The delivery unit 229 comprises a nozzleunit 231 which includes a nozzle 233 for delivering an aerosol spray ofsubstance, and a substance supply unit 235 for delivering a metered doseof substance to the nozzle unit 231.

In this embodiment the nozzle 233 of the nozzle unit 231 is directedtowards the nosepiece 225 and disposed so as to be co-axial therewith.

In this embodiment the substance supply unit 235 is an aerosol canisterfor delivering a metered volume of a propellant, preferably ahydrofluoroalkane (HFA) propellant or the like, containing substance,typically a medicament, either as a suspension or solution.

In an alternative embodiment the substance supply unit 235 couldcomprise a mechanical delivery pump, in particular a liquid deliverypump or a powder delivery pump, which delivers metered doses ofsubstance on actuation thereof.

The delivery unit 229 is primeable, in this embodiment by loading abiasing element, and includes a release mechanism, which, whentriggered, releases the biasing element and actuates the substancesupply unit 235 to deliver a metered dose of substance.

The delivery device further comprises a rotatable unit 236 whichcomprises first and second rotatable elements 237, 238 which are coupledby a link 239 such as to rotate in unison. One, the first, rotatableelement 237 is disposed downstream of the nozzle 233 of the nozzle unit231 such as to interact with an aerosol spray as generated from thenozzle 233, whereby an aerosol spray, when delivered from the nozzle233, is acted upon by the first rotatable element 237, in thisembodiment by reflection from the surface of the moving element 207 andinteraction with an interacting air flow as generated thereby, such asto optimize characteristics of the aerosol spray, and in particularmodify the particle size distribution of the particles of the aerosolspray and decelerate particles of the aerosol spray, which particles,once so optimized, are then entrained by the air flow through thechamber 223. The other, second rotatable element 238 is disposedupstream of the nozzle 233 of the nozzle unit 231 such as to be drivenby a delivered gas flow, in this embodiment an exhaled air flow, whichacts to drive the first rotatable element 237.

In this embodiment the first rotatable element 237 is mounted about acentral pivot 241 and includes a plurality of vanes 243 which areinclined in one sense such that rotation of the first rotatable element237 in one sense, in this embodiment in an anti-clockwise sense asviewed downstream, generates an interacting air flow in an upstreamdirection towards the nozzle 233 of the nozzle unit 231, whichinteracting air flow interacts with an aerosol spray as generated fromthe nozzle 233.

In this embodiment the second rotatable element 238 is mounted about acentral pivot 245 and includes a plurality of vanes 247 which areinclined in the other, opposite sense to the vanes 243 of the firstrotatable element 237 such that the exhaled air flow is such as to drivethe second rotatable element 238 in the one sense, that is, in acounter-clockwise sense as viewed downstream. This rotation of thesecond rotatable element 238 directly effects rotation of the firstrotatable element 237 in the same, one sense, which rotation of thefirst rotatable element 237 generates the interacting air flow in anupstream direction towards the nozzle 233 of the nozzle unit 231, whichinteracting air flow interacts with an aerosol spray as generated fromthe nozzle 233.

In this embodiment the first rotatable element 237 is configured to havea lesser resistance to air flow than the second rotatable element 238,and thereby the rotatable elements 237, 238 provide for a net flowthrough the chamber 223 and into the nasal airway 1 of the subject. Inthis embodiment the first rotatable element 237 includes vanes 243having greater pitch than the vanes 247 of the second rotatable element238. In an alternative embodiment the first rotatable element 237 couldhave a smaller diameter than the second rotatable element 238 such as toprovide an annular flow path about the inner periphery of the chamber223 for the exhaled air flow.

Operation of the delivery device will now be described hereinbelow.

Firstly, the nosepiece 225 is fitted to a nostril of a subject and themouthpiece 227 is gripped in the lips of the subject.

The subject then begins to exhale through the mouthpiece 227, whichexhalation acts to close the oropharyngeal velum of the subject anddeliver an air flow through the chamber 223 and the nasal airway 1 ofthe subject, which air flow acts to rotate the rotatable unit 236 by theaction of the air flow on the vanes 247 of the second rotatable element238. This rotation of the rotatable unit 236 causes the first rotatableunit 237 to generate an interacting air flow in an upstream directiontowards the nozzle 233 of the nozzle unit 231, which interacting airflow interacts with an aerosol spray as generated from the nozzle 233.

When a predetermined flow rate is achieved through the chamber 223, thesubstance supply unit 235 is actuated to deliver a metered dose ofsubstance through the nozzle 233 of the nozzle unit 231, which nozzle233 generates an aerosol spray in a direction towards the nosepiece 225.The aerosol spray, when delivered from the nozzle 233, is acted upon bythe first rotatable element 237, through reflection therefrom and theinteracting air flow generated thereby, such as to optimizecharacteristics of the particles thereof, in modifying the particle sizedistribution of the particles of the aerosol spray and decelerating theparticles of the aerosol spray, which particles, as so optimized, arethen entrained by the net air flow through the chamber 223.

In this way, the particles of the generated aerosol spray as deliveredto the nasal airway 1 have optimized characteristics, and in particularan optimized particle size distribution and a much reduced velocity.Optimizing the particle size distribution of the aerosol spray providesfor improved delivery to targeted sites in the nasal airway. Indecelerating the particles of the aerosol spray, deposition on unwantedsurfaces, which would result where the particles are delivered directlyfrom the nozzle 233 of the nozzle unit 231 without intervention, isavoided.

FIGS. 12( a) to (c) illustrate a nasal delivery device in accordancewith an eleventh embodiment of the present invention.

The delivery device comprises a chamber 253, in this embodiment asubstantially tubular member, into which an aerosol spray is delivered,a nosepiece 255 for fitting to a nostril of a subject which is in fluidcommunication with the chamber 253 and disposed to one, the downstream,end of the chamber 253, and a mouthpiece 257 through which the subjectexhales and which is in fluid communication with the chamber 253.

The delivery device further comprises a delivery unit 259 for deliveringan aerosol spray of substance into the chamber 253. The delivery unit259 comprises a nozzle unit 261 for delivering an aerosol spray ofsubstance, and a substance supply unit 265 for delivering a metered doseof substance to the nozzle unit 261.

In this embodiment the nozzle unit 261 includes a nozzle 267 fordelivering an aerosol spray of substance, and a tubular element 269which extends forwardly of the nozzle 267 and is disposed concentricallywithin the chamber 253 such as to define an annular flow path 271thereabout. The tubular element 269 includes a plurality of apertures273 at spaced locations along the length thereof for providing aplurality of flow paths from within the tubular element 269 to theannular flow path 271.

In this embodiment the nozzle 267 of the nozzle unit 261 is directedtowards the nosepiece 255 and disposed so as to be co-axial therewith.

In this embodiment the substance supply unit 265 is an aerosol canisterfor delivering a metered volume of a propellant, preferably ahydrofluoroalkane (HFA) propellant or the like, containing substance,typically a medicament, either as a suspension or solution.

In an alternative embodiment the substance supply unit 265 couldcomprise a mechanical delivery pump, in particular a liquid deliverypump or a powder delivery pump, which delivers metered doses ofsubstance on actuation thereof.

The delivery unit 259 is primeable, in this embodiment by loading abiasing element, and includes a release mechanism, which, whentriggered, releases the biasing element and actuates the substancesupply unit 265 to deliver a metered dose of substance.

The delivery device further comprises a rotatable element 277 which isdisposed at the distal end of the tubular element 269 of the nozzle unit261.

In this embodiment the rotatable element 277 is mounted about a centralpivot 281 and includes a plurality of first, outer vanes 283 which facethe downstream end of the annular flow path 271 such as to be acted uponby the exhaled air flow, and a plurality of second, inner vanes 285which are disposed radially inwardly of the outer vanes 283 and have aradial dimension corresponding to that of the tubular element 269 suchas to face the downstream end of the tubular element 269. The outervanes 283 of the rotatable element 277 are inclined in one sense suchthat the action of the exhaled air flow thereover causes the rotation ofthe rotatable element 277 in one sense, in this embodiment acounter-clockwise sense as viewed downstream. The inner vanes 285 of therotatable element 277 are inclined in the other, opposite sense to theouter vanes 283 such that rotation of the rotatable element 277 in theone sense causes the inner vanes 285 to generate an interacting air flowin an upstream direction into the tubular element 269 and towards thenozzle 267 of the nozzle unit 261, which interacting air flow interactswith an aerosol spray as generated from the nozzle 267, therebyoptimizing characteristics of the particles of the aerosol spray, incausing deceleration of the particles of the aerosol spray, and thedecelerated aerosol at least in part being entrained by the interactingair streams through the apertures 273 in the tubular element 269 andinto the annular flow channel 271 thereabout.

Operation of the delivery device will now be described hereinbelow.

Firstly, the nosepiece 255 is fitted to a nostril of a subject and themouthpiece 257 is gripped in the lips of the subject.

The subject then begins to exhale through the mouthpiece 257, whichexhalation acts to close the oropharyngeal velum of the subject anddeliver an air flow through the chamber 253 via the annular flow channel271 and the nasal airway 1 of the subject, which air flow acts to rotatethe rotatable element 277 in the one sense, in this embodiment thecounter-clockwise as viewed downstream, by the action of the exhaled airflow over the outer vanes 283 of the rotatable element 277. Thisrotation of the rotatable element 277 causes the inner vanes 285 togenerate an interacting air flow in an upstream direction towards thenozzle 267 of the nozzle unit 261, which interacting air flow interactswith an aerosol spray as generated from the nozzle 267.

When a predetermined flow rate is achieved through the chamber 253, thesubstance supply unit 265 is actuated to deliver a metered dose ofsubstance through the nozzle 267 of the nozzle unit 261, which nozzle267 generates an aerosol spray in a direction towards the nosepiece 255.The aerosol spray, when delivered from the nozzle 267 of the nozzle unit261, is acted on by the interacting air flow generated by the innervanes 285 of the rotatable element 277 such as to decelerate theparticles of the aerosol spray, and in a preferred embodiment modify theparticle size distribution of the particles of the aerosol spray, whichparticles are then entrained by the interacting air flow as air flowsthrough the apertures 273 in the tubular element 269 and into theannular flow channel 271 thereabout, and subsequently entrained by theexhaled air flow through the chamber 253 and the nasal airway 1 of thesubject.

In this way, the particles of the generated aerosol spray as deliveredto the nasal airway 1 have optimized characteristics, and in particularan optimized particle size distribution and a much reduced velocity.Optimizing the particle size distribution of the aerosol spray providesfor improved delivery to targeted sites in the nasal airway. Indecelerating the particles of the aerosol spray, deposition on unwantedsurfaces, which would result where the particles are delivered directlyfrom the nozzle 267 of the nozzle unit 261 without intervention, isavoided.

Finally, it will be understood that the present invention has beendescribed in its preferred embodiments and can be modified in manydifferent ways without departing from the scope of the invention asdefined by the appended claims.

For example, the nasal delivery device of the above-described fourthembodiment could be modified in the manner of the above-described thirdembodiment, that is, to include an exhalation breath-actuatable gassupply unit 85 for delivering a gas flow through the chamber 93 which isseparate to the exhalation breath of a subject.

In preferred embodiments the delivery devices are configured to deliversubstance through one nostril of a subject at such a pressure as to flowaround the posterior margin of the nasal septum 4 and out of the othernostril of the subject, thereby achieving bi-directional deliverythrough the nasal cavities 2, 3 as disclosed in WO-A-00/51672. Inalternative embodiments the delivery devices can be configured todeliver substance at a reduced pressure which is not sufficient toachieve bi-directional delivery through the nasal cavities 2, 3.

1. A nasal delivery device for delivering substance to a nasal airway ofa subject, comprising: a nosepiece for fitting to a nostril of asubject; a delivery unit comprising a substance supply unit and a nozzleunit including at least one nozzle fluidly connected to the substancesupply unit for generating an aerosol spray for delivery to a nasalairway of the subject; and an aerosol interactor operable to interactwith an aerosol spray as generated by the at least one nozzle.
 2. Thedelivery device of claim 1, wherein the aerosol interactor is configuredsuch that operation thereof is actuated prior to actuation of thedelivery unit.
 3. The delivery device of claim 1, wherein the at leastone nozzle is configured such as to deliver the aerosol spray towardsthe nosepiece.
 4. The delivery device of claim 1, wherein the aerosolinteractor comprises a flow director for directing an interacting gasflow at the aerosol spray such as to interact with the same.
 5. Thedelivery device of claim 4, wherein the flow director includes at leastone flow-directing channel downstream of the at least one nozzle fordirecting an interacting gas flow and delivering at least oneinteracting gas stream to interact with the aerosol spray.
 6. Thedelivery device of claim 5, wherein the at least one flow-directingchannel has an annular outlet disposed about a delivery path of theaerosol spray.
 7. The delivery device of claim 6, wherein the at leastone flow-directing channel is configured such as to direct the at leastone interacting gas stream substantially orthogonally to the deliverypath of the aerosol spray.
 8. The delivery device of claim 6, whereinthe at least one flow-directing channel is configured such as to directthe at least one interacting gas stream in a direction inclined to thedelivery path of the aerosol spray and away from the nosepiece.
 9. Thedelivery device of claim 8, wherein the at least one flow-directingchannel is an annular, frusto-conical channel configured to deliver aconical, annular interacting gas stream to the delivery path of theaerosol spray.
 10. The delivery device of claim 9, wherein the at leastone flow-directing channel is configured such that an apex of theconical, annular interacting gas stream delivered thereby is co-incidentwith the delivery path of the aerosol spray.
 11. The delivery device ofclaim 4, further comprising: a chamber in fluid communication with thenosepiece; and wherein the flow director includes an annular flowchannel for providing an annular gas flow over an inner periphery of thechamber.
 12. The delivery device of claim 11, wherein the chamberincludes a flow deflector disposed at the inner periphery thereof anddownstream of the at least one nozzle which is such as to obstruct theannular gas flow generated at the inner periphery of the chamber andcause the same to be deflected inwardly and generate a turbulent zonedownstream of the at least one nozzle.
 13. The delivery device of claim12, wherein the flow deflector comprises an annular member.
 14. Thedelivery device of claim 4, wherein the flow director includes aplurality of flow-directing channels in spaced relation downstream ofthe at least one nozzle for directing an interacting gas flow anddelivering a plurality of interacting gas streams to interact with theaerosol spray.
 15. The delivery device of claim 1, further comprising: amouthpiece through which the subject in use exhales.
 16. (canceled) 17.(canceled)
 18. The delivery device of claim 1, wherein the aerosolinteractor comprises a movable element disposed downstream of the atleast one nozzle.
 19. The delivery device of claim 18, wherein theaerosol interactor is disposed in opposed relation to the at least onenozzle.
 20. The delivery device of claim 19, wherein the aerosolinteractor is configured such as to present a continuous surface to theaerosol spray.
 21. The delivery device of claim 18, wherein the aerosolinteractor is disposed relative to the at least one nozzle such that theaerosol spray is reflected thereby.
 22. The delivery device of any ofclaim 18, wherein the movable element comprises a rotatable element. 23.The delivery device of any of claim 18, wherein the movable elementcomprises first and second rotatable elements coupled so as to rotate inunison, the first rotatable element including vanes oriented in onesense such as to be rotated in one sense by a gas flow thereover, andthe second rotatable element being disposed downstream of the at leastone nozzle and including vanes oriented in the other, opposite sense tothe vanes of the first rotatable element such as to generate aninteracting gas flow in an upstream direction towards the at least onenozzle on being rotated in the one sense by rotation of the firstrotatable element.
 24. The delivery device of claim 23, wherein thefirst rotatable element is disposed upstream of the at least one nozzle.25. The delivery device of any of claim 18, wherein the nozzle unitincludes a tubular element which extends downstream of the at least onenozzle and includes a plurality of apertures for providing a pluralityof flow paths therethrough, and the aerosol interactor comprises arotatable element disposed at a downstream end of the tubular element,the rotatable element including first, outer vanes oriented in one senseand disposed radially beyond the tubular element such that the rotatableelement is rotated in one sense by a gas flow thereover, and second,inner vanes oriented in the other, opposite sense to the outer vanessuch as to generate an interacting gas flow in an upstream directiontowards the at least one nozzle with rotation of the rotatable element,which interacting gas flow is such as to interact with the aerosol sprayand pass through the apertures in the tubular element.
 26. The deliverydevice of claim 1, wherein the substance supply unit comprises anaerosol canister.
 27. The delivery device of claim 1, wherein thesubstance supply unit comprises a delivery pump.
 28. The delivery deviceof claim 27, wherein the delivery pump comprises a liquid spray pump.29. A method of delivering substance to a nasal airway of a subject,comprising the steps of: fitting a nosepiece to a nostril of a subject;actuating a delivery unit to generate an aerosol spray from at least onenozzle for delivery to a nasal airway of the subject; and operating anaerosol interactor to interact with an aerosol spray as generated by theat least one nozzle.
 30. The method of claim 29, wherein operation ofthe aerosol interactor is actuated prior to actuation of the deliveryunit.
 31. The method of claim 29, wherein the aerosol spray is deliveredtowards the nosepiece.
 32. The method of any of claim 29, wherein theaerosol interactor comprises a flow director; and the step of operatingthe aerosol interactor comprises the step of: directing an interactinggas flow at the aerosol spray such as to interact with the same.
 33. Themethod of claim 32, wherein the flow director includes at least oneflow- directing channel downstream of the at least one nozzle, and thestep of operating the aerosol interactor comprises the step of:directing an interacting gas flow to deliver at least one interactinggas stream, to interact with the aerosol spray.
 34. The method of claim33, wherein the at least one flow-directing channel has an annularoutlet disposed about a delivery path of the aerosol spray.
 35. Themethod of claim 34, wherein the at least one interacting gas stream isdirected substantially orthogonally to the delivery path of the aerosolspray.
 36. The method of claim 34, wherein the at least one interactinggas stream is directed in a direction inclined to the delivery path ofthe aerosol spray and away from the nosepiece.
 37. The method of claim36, wherein the at least one interacting gas stream is a conical,annular interacting gas stream.
 38. The method of claim 37, wherein anapex of the conical, annular interacting gas stream is co-incident withthe delivery path of the aerosol spray.
 39. The method of claim 32,wherein the aerosol spray is delivered into a chamber in fluidcommunication with the nosepiece; and further comprising the step of:providing an annular gas flow over an inner periphery of the chamber.40. The method of claim 39, wherein the chamber includes a flowdeflector disposed at the inner periphery thereof and downstream of theat least one nozzle; and further comprising the step of: obstructing theannular gas flow generated at the inner periphery of the chamber such asto cause the same to be deflected inwardly and generate a turbulent zonedownstream of the at least one nozzle.
 41. The method of claim 40,wherein the flow deflector comprises an annular member.
 42. The methodof claim 32, wherein the flow director includes a plurality offlow-directing channels in spaced relation downstream of the at leastone nozzle, and the step of operating the aerosol interactor comprisesthe step of: directing an interacting gas flow to deliver a plurality ofinteracting gas streams to interact with the aerosol spray.
 43. Themethod of claim 29, further comprising the step of: the subject exhalingthrough a mouthpiece.
 44. (canceled)
 45. (canceled)
 46. The method ofclaim 29, wherein the aerosol interactor comprises a movable elementdisposed downstream of the at least one nozzle; and the step ofoperating the aerosol interactor comprises the step of: moving themovable element downstream of the at least one nozzle such as tointeract with the aerosol spray.
 47. The method of claim 46, wherein theaerosol interactor is disposed in opposed relation to the at least onenozzle.
 48. The method of claim 47, wherein the aerosol interactor isconfigured such as to present a continuous surface to the aerosol spray.49. The method of claim 47, wherein the aerosol interactor is disposedrelative to the at least one nozzle such that the aerosol spray isreflected thereby.
 50. The method of claim 46, wherein the movableelement comprises a rotatable element.
 51. The method of claim 46,wherein the movable element comprises first and second rotatableelements coupled so as to rotate in unison, the first rotatable elementincluding vanes oriented in one sense such as to be rotated in one senseby a gas flow thereover, and the second rotatable element being disposeddownstream of the at least one nozzle and including vanes oriented inthe other, opposite sense to the vanes of the first rotatable elementsuch as to generate an interacting gas flow in an upstream directiontowards the at least one nozzle on being rotated in the one sense byrotation of the first rotatable element; and further comprising the stepof: driving a gas flow over the first rotatable element such as to causerotation of the same and thereby rotate the second rotatable elementsuch as to generate an interacting gas flow in an upstream directiontowards the at least one nozzle.
 52. The method of claim 51, wherein thefirst rotatable element is disposed upstream of the at least one nozzle.53. The method of claim 46, wherein the step of actuating the deliveryunit to generate an aerosol spray comprises the step of: actuating thedelivery unit to generate an aerosol spray from at least one nozzle intoa tubular element which extends downstream of the at least one nozzle,the tubular element including a plurality of apertures for providing aplurality of flow paths therethrough; the step of operating the aerosolinteractor comprises the step of: moving a rotatable element disposed ata downstream end of the tubular element, the rotatable element includingfirst, outer vanes oriented in one sense and disposed radially beyondthe tubular element such that the rotatable element is rotated in onesense by a gas flow thereover, and second, inner vanes oriented in theother, opposite sense to the outer vanes such as to generate aninteracting gas flow in an upstream direction towards the at least onenozzle with rotation of the rotatable element; and further comprisingthe step of: driving a gas flow over the outer vanes of the rotatableelement to cause rotation of the same and thereby cause the inner vanesof the rotatable element to generate an interacting gas flow in anupstream direction towards the at least one nozzle, which interactinggas flow is such as to interact with the aerosol spray and pass throughthe apertures in the tubular element.
 54. The method of claim 29,wherein the aerosol spray is from an aerosol canister.
 55. The method ofclaim 29, wherein the aerosol spray is from a delivery pump.
 56. Themethod of claim 55, wherein the delivery pump comprises a liquid spraypump.
 57. (canceled)
 58. (canceled)